B lymphocytes respond to antigen by proliferating and differentiating into antibody-secreting plasmacytes. That response can be enhanced, or inhibited by antigen-specific T helper (TH) or T suppressor (TS) cells, respectively. The TNP-specific IgA315-secreting MOPC-315 myeloma plasma cells arise by differentiation from malignant small, nonsecretory lymphocytoid stem cells. The proliferation and differentiation of those stem cells can be regulated by distinct subsets of carrier-specific TH and TS cells. We also have shown that anti-Lyb3 and anti-Lyb2.2 specifically counteract suppression of MOPC-315 cell secretory differentiation and proliferation, respectively. Experiments are planned to determine the genetic restrictions of the various regulatory cells, their effects on cell cycle progression and the role of cyclic nucleotide pathways in regulation of B cell growth and differentiation.